Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort

Owei, Ibiye; Umekwe, Nkiru; Stentz, Frankie B.; Wan, Jim Y.; Dagogo‐Jack, Samuel

doi:10.1016/j.metabol.2019.06.011

Cited by 32 publications

(29 citation statements)

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Section: Discussionsupporting

confidence: 86%

“…BMI and levels of both branched-chain and aromatic AAs were significantly positively associated in both sexes. These findings were also demonstrated in previous studies focusing on obesity in adults [15,16] and individuals with type 2 diabetes [6,8,17] as well as in studies focusing on obesity in children [18,19]. McCormack et al and Perng et al also indicated that elevated levels of BCAAs are significantly positively associated with obesity in children and adolescents [18,19].…”

Section: Discussionsupporting

confidence: 71%

“…To the best of our knowledge, this is the first study of a large pediatric cohort in a Caucasian/German population investigating physiological AA and AC concentrations and associations with biochemical parameters. The strengths of our study include the number of metabolites investigated, i.e., 30 (23 AAs,6 ACs, and free carnitine) and the large sample size (2191 subjects aged 3 months to 18 years; 3989 DBS samples). A further strength of the LIFE Child cohort is the availability of data regarding the participants' puberty status and BMI, and concentrations of key metabolic serum markers.…”

Section: Discussionmentioning

confidence: 99%

“…In newborn screening, concentrations of amino acids (AAs) and acylcarnitines (ACs) are measured in dried blood spots (DBS) using tandem mass spectrometry to diagnose a variety of congenital metabolic disorders such as organic acidemia, aminoacidopathies, fatty acid oxidation disorders, carnitine cycle disorders, and some urea cycle disorders [3,4]. Previous studies have also investigated whether AAs and ACs can function as predictors of complex metabolic diseases in adults (e.g., type 2 diabetes, cardiovascular disease, obesity) [5][6][7][8]. More recently, metabolomics has also been applied in pediatric cohorts to identify biomarkers for predicting metabolic imbalances (e.g., early insulin resistance) or diseases [2,9,10].…”

Section: Introductionmentioning

confidence: 99%

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Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

et al. 2020

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Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

et al. 2020

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“…Amino acids are key substances of protein, and thus, the body. Some studies have shown that elevated levels of amino acids in plasma could not only reflect IR, the lack of relative insulin, and the decrease of amino acid catabolism, but also induce IR through the activation of mTOR, AMPK, and other signaling pathways (Owei, Umekwe, Stentz, Wan, & Dagogo-Jack, 2019). Numerous studies have revealed that the concentration of extracellular amino acids is a signal factor for in vivo protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

Zanthoxylum alkylamides improve amino acid metabolism in type 2 diabetes mellitus rats

et al. 2020

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To investigate the effect of Zanthoxylum alkylamides (ZA) on amino acid metabolism of type 2 diabetes mellitus (T2DM), the present study was performed with T2DM rats model induced with high fat and sugar fodder combined with low-dose of streptozotocin. ZA were fed to rats at three different doses of 2, 4, and 8 mg/kg for 28 days and metformin was fed to rats at 135 mg/kg as positive control. The results showed that compared with the normal control, the amino acid levels and the expression of related carrier genes were disordered in T2DM rats. Compared with the model, different doses of ZA could significantly resist (p < .05) the decrease in body weight of T2DM rats and improve hyperglycemia, with the best result observed with the high dose (8 mg/kg). Different doses of ZA could ameliorate the levels of 19 kinds of amino acid in the plasma, jejunum, liver, and skeletal muscle of T2DM rats by regulating the expression of related amino acid transporters including LAT1, SNAT2, CAT1, et al. to thereby ameliorating amino acid metabolism disorder in T2DM rats. Practical applications Previous studies showed that Zanthoxylum alkylamides (ZA) could promote the amino acid metabolism in the jejunum of healthy SD rats, improve protein metabolism disorder of type 1 diabetic rats, and also reduce the risk of metabolic syndrome in fat rats model. Herein, we investigated the effect of ZA on amino acid metabolism in type 2 diabetes mellitus (T2DM) rats. The results indicated that ZA could remarkably improve the abnormal expression of amino acid carriers in the jejunum, liver, and skeletal muscle, thereby ameliorating the disorder of amino acid metabolism in the plasma, jejunum, liver, and skeletal muscle of T2DM rats. Therefore, ZA are potential antidiabetic food/medicine product for the T2DM treatment.

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Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

et al. 2022

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Purpose of Review Diabetes mellitus is a complex, chronic illness characterized by elevated blood glucose levels that occurs when there is cellular resistance to insulin action, pancreatic β-cells do not produce sufficient insulin, or both. Diabetes prevalence has greatly increased in recent decades; consequently, it is considered one of the fastest-growing public health emergencies globally. Poor blood glucose control can result in long-term micro- and macrovascular complications such as nephropathy, retinopathy, neuropathy, and cardiovascular disease. Individuals with diabetes require continuous medical care, including pharmacological intervention as well as lifestyle and dietary changes. Recent Findings The most common form of diabetes mellitus, type 2 diabetes (T2DM), represents approximately 90% of all cases worldwide. T2DM occurs more often in middle-aged and elderly adults, and its cause is multifactorial. However, its incidence has increased in children and young adults due to obesity, sedentary lifestyle, and inadequate nutrition. This high incidence is also accompanied by an estimated underdiagnosis prevalence of more than 50% worldwide. Implementing successful and cost-effective strategies for systematic screening of diabetes mellitus is imperative to ensure early detection, lowering patients' risk of developing life-threatening disease complications. Therefore, identifying new biomarkers and assay methods for diabetes mellitus to develop robust, non-invasive, painless, highly-sensitive, and precise screening techniques is essential. Summary This review focuses on the recent development of new clinically validated and novel biomarkers as well as the methods for their determination that represent cost-effective alternatives for screening and early diagnosis of T2DM.

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Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort

Cited by 32 publications

References 50 publications

Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents

Zanthoxylum alkylamides improve amino acid metabolism in type 2 diabetes mellitus rats

Recent Developments in Biomarkers for Diagnosis and Screening of Type 2 Diabetes Mellitus

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